The Section leads novel clinical trials and conducts correlative biologic studies and pre-clinical investigations into the biology of leukemias and lymphomas in collaboration with intramural and extramural investigators. A major focus of the Hematologic Diseases Section research program is the development of targeted agents for childhood leukemias and lymphomas. Among the most active programs is the study of anti-CD22 immunotoxin agents RFB4(dsFv)-PE38 developed at the NCI in the therapy of drug-resistant acute lymphoblastic leukemia (ALL). A pediatric Phase I trial of a first-generation agent (BL22, CAT-3888) was conducted at the NCI (Wayne et al, Clin Cancer Res 2010;16:1894). BL22 was shown to have an acceptable safety profile and clinical activity was observed in children with multiply relapsed chemotherapy resistant ALL. Studies of a modified agent with higher CD22 binding affinity (moxetumomab pasudotox, HA22, CAT-8015) showed improved in vitro cytotoxicity against childhood ALL blasts (Mussai et al, Br J Haematol 2010, Epub ahead of print 2010 Jun 7, PMID: 20528877). A pediatric Phase I trial of HA22 is in progress at the NCI, St. Jude Childrens Research Hospital, and the Dana-Farber Cancer Institute/Childrens Hospital, Boston. Complete remissions in chemotherapy-refractory ALL have been achieved with this new agent (Wayne et al, Blood 2009;114(22):345a;Wayne et al, Blood 2010;116:3246a;Wayne et al, Blood 2011;118:1317a;Shah et al, Biol Blood Marrow Transplant 2012;18(2), Suppl 2:S234). Another major area of investigation is in allogeneic hematopoietic stem cell transplantation (AlloSCT) for pediatric leukemias and lymphomas. Relapse remains a major cause of failure of AlloSCT in the treatment of children and adolescents with leukemia. The Section investigates methods to direct allogeneic anti-cancer responses in attempt to enhance graft-versus-leukemia effects after AlloSCT. The Section also serves in a leadership role in a broad NCI program that addresses the problem of relapse after AlloSCT. These efforts include an NCI-sponsored International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation (Bishop et al, Biol Blood Marrow Transplant 2010;16:564) and specific studies of the natural history, biology, and treatment of relapse after AlloSCT. The clinical trial development activities of the Section are conducted in collaboration with a number of pediatric oncology consortia and cooperative groups including the Childrens Oncology Group and the Pediatric Blood and Marrow Transplant Consortium.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICSC010353-14
Application #
8763795
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2013
Total Cost
$666,058
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Mehta, Neha; Wayne, Alan S; Kim, Youn H et al. (2012) Bexarotene is active against subcutaneous panniculitis-like T-cell lymphoma in adult and pediatric populations. Clin Lymphoma Myeloma Leuk 12:20-5
Wei, Hui; Xiang, Laiman; Wayne, Alan S et al. (2012) Immunotoxin resistance via reversible methylation of the DPH4 promoter is a unique survival strategy. Proc Natl Acad Sci U S A 109:6898-903
Larochelle, Andre; Gillette, Jennifer M; Desmond, Ronan et al. (2012) Bone marrow homing and engraftment of human hematopoietic stem and progenitor cells is mediated by a polarized membrane domain. Blood 119:1848-55
Shah, Nirali N; Bacher, Ulrike; Fry, Terry et al. (2012) Myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: diagnostic and therapeutic challenges. Am J Hematol 87:916-22
Cohen, Jeffrey I; Jaffe, Elaine S; Dale, Janet K et al. (2011) Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood 117:5835-49
El-Mallawany, N K; Geller, L; Bollard, C M et al. (2011) Long-term remission in a child with refractory EBV(+) hydroa vacciniforme-like T-cell lymphoma through sequential matched EBV(+)-related allogeneic hematopoietic SCT followed by donor-derived EBV-specific cytotoxic T-lymphocyte immunotherapy. Bone Marrow Transplant 46:759-61
Bishop, Michael R; Alyea 3rd, Edwin P; Cairo, Mitchell S et al. (2011) National Cancer Institute's First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: summary and recommendations from the organizing committee. Biol Blood Marrow Transplant 17:443-54
Zhang, Hua; Cui, Yongzhi; Voong, Nga et al. (2011) Activating signals dominate inhibitory signals in CD137L/IL-15 activated natural killer cells. J Immunother 34:187-95
Sokolic, Robert; Maric, Irina; Kesserwan, Chimene et al. (2011) Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency. Blood 118:2688-94
Jasper, Gregory A; Arun, Indu; Venzon, David et al. (2011) Variables affecting the quantitation of CD22 in neoplastic B cells. Cytometry B Clin Cytom 80:83-90

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